Castanospermine is an inhibitor of α- and β-glucosidases (Saul, R., Ghidoni, J. J., Molyneux, R. J., et al. (1985) Proc Natl Acad Sci USA, 82, 93-97). Glucosidases catalyze the cleavage of individual glucosyl residues from various glycoconjugates, including complex carbohydrates and glycoproteins. Glucose residues found on high mannose glycoprotein oligosaccharides must first be cleaved before they are further processed to yield complex type oligosaccharide structures. Inhibition of glycoprotein oligosaccharide processing can affect protein trafficking and cell functions that are dependent on glycosylation, including angiogenesis (Pili, R., Chang, J., Partis, R. A., et al. (1995) Cancer Res., 55, 2920-2926). Castanospermine also interferes with viral replication and infection that is dependent on glucosidase activity (Montefiori, D. C., Robinson, W. E., and Mitchell, W. M. (1988) Proc Natl Acad Sci USA, 85, 9248-9252; Walker, B. D., Kowalski, M., Goh, W. C., et al. (1987) Proc Natl Acad Sci USA, 84, 8120-8124). Evidence of castanospermine's antiviral activity has been reported for Dengue virus (Whitby, K., Pierson, T. C., Geiss, B., et al. (2005) J Virol, 79, 8698-8706; Courageot, M-P, Frenkiel, M-P, et al. (2000) J Virol, 74, 564-572). Dengue virus is spread via mosquitoes and results in Dengue fever, the most prevalent mosquito borne human disease. Dengue virus is an enveloped single-stranded, positive-sense RNA virus of the genus Flavivirus. The Dengue virus RNA is translated in the cytoplasm as a single polyprotein that is cleaved into three structural and seven nonstructural proteins. There are four related serotypes that are transmitted to humans primarily by two mosquitoes, Aedes aegypti and Aedes albopictus. 
Assembly of the Dengue virus in infected cells takes place at the endoplasmic reticulum (ER). The viral structural glycoproteins prM and E localize to the luminal side of the ER and form an immature particle with prM and E in a heterodimeric complex. Proteolysis of prM in the trans-Golgi network triggers rearrangement, homodimerization of E, and formation of the mature viral particle before release from the infected cell. During normal virus assembly in mammalian cells a 14-residue oligosaccharide, (Glc)3(Man)9(GlcNAc)2, is added in the ER to specific asparagine residues on the prM and E proteins. This high-mannose carbohydrate is normally sequentially modified in the ER by resident α-glucosidases to generate N-linked glycans that lack the terminal α1,2- and both α1,3-glucose residues which are then normally converted to complex-type oligosaccharide moieties. This processing of N-linked carbohydrates in the ER is required for proper assembly and secretion of the Dengue virus (Courageot, M-P, Frenkiel, M-P, et al. (2000) J Virol, 74, 564-572; Wu, S. F., C. J. Lee, C. L. Liao et al. (2002) J. Virol., 76, 3596-3604). It is believed that the effect of castanospermine on normal glycoprotein processing inhibits secretion and infectivity of Dengue viral particles. These antiviral properties may have utility in treating Dengue virus infections in humans (Whitby, K., Pierson, T. C., Geiss, B., et al. (2005) J Virol, 79, 8698-8706).
Other viruses that are genetically related to Dengue virus are known to cause yellow fever, hepatitis C, and the Japanese, St. Louis, and West Nile encephalitis. Studies of Japanese encephalitis virus with a different α-glucosidase inhibitor, N-nonyl-deoxynojirimycin (NN-DNJ), suppressed cell infection but to a lesser extent than with Dengue virus (Wu, S. F., C. J. Lee, C. L. Liao et al. (2002) J. Virol., 76, 3596-3604). In these experiments, there was a decreased mortality rate among mice given a lethal dose of Japanese encephalitis virus upon treatment with NN-DNJ. Thus, at least some flaviviruses appear sensitive to alpha-glucosidase inhibitors, such as castanospermine and deoxynojirimycin (Whitby, K., Pierson, T. C., Geiss, B., et al. (2005) J Virol, 79, 8698-8706). West Nile Virus is one Flavivirus that is insensitive to castanospermine. Other studies have documented that alpha-glucosidase inhibitors reduce infection of some RNA and DNA viruses (McGinnes, L. W., and T. G. Morrison (1998) Virus Res, 53, 175-185).
The Zika virus is a Flavivirus that is spread to humans through mosquito bites. It is presently a major human health concern. Although Zika virus infection often causes no or only mild symptoms, Zika virus may spread from a pregnant women to the baby resulting in microcephaly and other severe brain problems. Further, the World Health Organization (WHO) indicates there is strong scientific consensus that Zika virus infections in adults can result in Guillain-Barré syndrome, a neurological syndrome that can cause temporary paralysis. Zika virus prevalence is highest within a narrow equatorial belt from Africa to Asia. In the United States, Zika virus is found in Florida and portions of other states bordering on the Gulf of Mexico. Overall, there are over 2 billion people that live in regions of the world impacted by the Zika virus. There are presently no vaccines or medications capable of preventing or treating Zika virus infections.